The administration of anxiolytic drugs often accompanies treatment with antidepressant medications. Although benzodiazepines help alleviate the secondary depressive symptoms of anxiety and sleep disturbance, they do not actually enhance antidepressant response. On the other hand, the anxiolytic agent buspirone does facilitate direct antidepressant response, largely through its ability to activate both presynaptic and postsynaptic 5-HT1A receptors and thus modulate serotonin release. Several case studies and open-label trials have demonstrated the effectiveness of buspirone as an augmentation agent. Because buspirone is also associated with few adverse effects, it appears to be both effective and safe in the augmentation of antidepressant pharmacotherapy.